Chronic consumption of salt is well known as a cause of high blood pressure, but only recently, scientists have suggested that sodium chloride may play a role in triggering autoimmune diseases, which can be very serious. This involves the overproduction of immune-system cells that attack an organism’s own tissues, according to a recent article in the journal Nature
The incidence of autoimmune diseases, such as multiple sclerosis and type-1 diabetes, has spiked in developed countries in recent decades. In three studies in the prestigious journal, researchers describe the molecular pathways that can lead to autoimmune disease and identify one possible culprit that has been right under our noses – and on our tables – the entire time: salt.
To stay healthy, the human body relies on a careful balance; if we have a weak immune system, we are more likely to succumb to infection, but if there is too much activity and the immune system begins to attack healthy tissue, this results in autoimmunity. Some forms of autoimmunity have been linked to overproduction of TH17 cells, a type of helper T cell that produces an inflammatory protein called interleukin-17. But finding the molecular switches that cause the body to overproduce TH17 cells has been difficult, in part because conventional methods of activating native immune cells in the laboratory often harm the cells or alters the course of their development.
So when researchers heard a talk by Harvard physicist Hongkun Park about the use of silicone nanowires to disarm single genes in cells, they approached him immediately, recalls Prof. Aviv Regev, a computational biologist at the nearby Massachusetts Institute of Technology. Regev completed her doctorate at Tel Aviv University under the supervision of Profs. Eva Jablonka and Ehud Shapiro and was awarded the Overton Prize in 2008 for “outstanding accomplishment to a scientist in the early to mid stage of his or her career” and co-authored on two of the studies.
Park showed last year that these can be used to manipulate genes in immune cells without affecting the cells’ functions. For the first of the Nature studies, Regev and her colleagues used Park’s technology to piece together a functional model of how TH17 cells are controlled, she says. “Otherwise,” she explains, they would have been only “guessing in the dark.”
In the second study, an affiliated team of researchers observed immune cell production over 72 hours. One protein kept cropping up as a TH17 signal – serum glucocorticoid kinase 1 (SGK1), which is known to regulate salt levels in other types of cells. The researchers found that mouse cells cultured in high salt conditions had higher SGK1 expression and produced more TH17 cells than those grown in normal conditions.
“If you incrementally increase salt, you get generation after generation of these TH17 cells,” says study co-author Vijay Kuchroo, an immunologist at Brigham and Women’s Hospital in Boston, Massachusetts. In the third study, researchers confirmed Kuchroo’s findings, in mouse and human cells. It was “an easy experiment – you just add salt,” says Hafler, a neurologist at Yale University who led the research.
But could salt change the course of autoimmune disease? Both Kuchroo and Hafler found that in a mouse model of multiple sclerosis, a high-salt diet accelerated the disease’s progression.
All this evidence, Kuchroo says, “is building a very interesting hypothesis [that] salt may be one of the environmental triggers of autoimmunity.”
But Kuchroo and other researchers say that evidence so far cannot predict the effect of salt on human autoimmunity.
“As a physician, I’m very cautious,” Hafler says. “Should patients go on a low-salt diet? Yes,” he says, adding that “people should probably already be on a low-salt diet” for general health concerns. Hafler and others note, however, that there are likely many cell types and environmental factors involved in triggering autoimmunity.
The results offer tantalizing leads for drug targets for autoimmune conditions, but O’Shea notes that it is unclear whether TH17 proliferation is a factor in all autoimmune disease. A targeted drug that might work to relieve psoriasis might not subdue rheumatoid arthritis.
“When we say autoimmunity, we’re implying that it’s one thing,” O’Shea says. “But it’s not one thing – it’s heterogeneous.”
ASPIRIN MAY LOWER MELANOMA RISK A new study has found that women who take aspirin have a reduced risk of developing melanoma and that the longer they take it, the lower the risk. The findings suggest that aspirin’s anti-inflammatory effects may help protect against this type of skin cancer. The study is published early online in Cancer, a peer-reviewed journal of the American Cancer Society.
In the Women’s Health Initiative, researchers observed US women aged 50 to 79 years for an average of 12 years and noted which individuals developed cancer. At the beginning of the study, the women were asked which medications they took, what they ate and what activities they performed.
When Dr. Jean Tang of California’s Stanford University School of Medicine and her colleagues analyzed available data from 59,806 Caucasian women in the study, they found that women who took more aspirin were less likely to develop melanoma skin cancer during the 12 years of follow-up. Overall, women who used aspirin had a 21 percent lower risk of melanoma relative to non-users.
Each incremental increase in duration of aspirin use (less than one year of use, one to four years of use, and five or more years of use) was associated with an 11% lower risk of melanoma. Thus, women who used aspirin for five or more years had a 30% lower melanoma risk than women who did not use aspirin. The researchers controlled for differences in pigmentation, tanning practices, sunscreen use and other factors that may affect skin cancer risk.
“Aspirin works by reducing inflammation, and this may be why using aspirin may lower your risk of developing melanoma,” said Tang. Other pain medications, such as acetaminophen, did not lower women’s melanoma risk. Tang noted that the findings support the design of a clinical trial to directly test whether aspirin can be taken to prevent melanoma.
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